A virulent isolate of Pseudomonas aeruginosa was obtained by passing avirulent bacteria (strain PAO-1) through sequential infections in compromised mice. Iron and methotrexate were used to compromise the mice and the resultant virulent bacteria expressed changes from avirulent bacteria in iron metabolism. The interactions of avirulent and virulent bacteria with the bacterial siderophores, pyochelin and pyoverdin, are being studied. This study includes growth measurements and 55Fe uptake assays in the presence of transferrin and other chelators. Identification of the biosynthetic pathways for pyochelin and pyoverdin, and the enzymatic reactions with ferrisiderophores are areas for investigation. Mice are capable of clearing 10 to the 6th power P. aeruginosa from blood and organs within 12 hours after injection. The transferrin system in mouse serum and mouse leukocytes are being examined for bacteriostatic and bactericidal activities against virulent and avirulent P. aeruginosa. The physiological expressions of virulent bacteria will be compared with physiological traits of other P. aeruginosa isolated from human infections.